Hydrophilic coating

ABSTRACT

The invention relates to a coating formulation for preparing a hydrophilic coating, wherein the hydrophilic coating formulation comprises a supporting monomer and/or polymer comprising at least 2 reactive moieties capable of undergoing polymerization reactions, a polyelectrolyte, a Norrish Type I photoinitiator, and a Norrish Type II photoinitiator.

This invention relates to a hydrophilic coating formulation forpreparing a hydrophilic coating. The invention further relates to acoating system, a hydrophilic coating, a lubricious coating, use of aNorrish Type 1 and a Norrish Type II photoinitiator in a lubriciouscoating, an article, a medical device or component and a method offorming a hydrophilic coating on a substrate.

Many medical devices, such as guide wires, urinary and cardiovascularcatheters, syringes, and membranes need to have a lubricant applied tothe outer and/or inner surface to facilitate insertion into and removalfrom the body and/or to facilitate drainage of fluids from the body.Lubricious properties are also required so as to minimize soft tissuedamage upon insertion or removal. Especially, for lubrication purposes,such medical devices may have a hydrophilic surface coating or layerwhich becomes lubricious and attains low-friction properties uponwetting, i.e. applying a wetting fluid for a certain time period priorto insertion of the device into the body of a patient. A coating orlayer which becomes lubricious after wetting is hereinafter referred toas a hydrophilic coating. A coating obtained after wetting ishereinafter referred to as a lubricious coating.

It has now been observed that such lubricious coatings are often proneto wear and as such may lose coating material in the tortuous path (e.g.in a blood vessel). Moreover, they may lose their lubricious propertiesupon use.

Therefore it is an object of the present invention to provide alubricious coating that exhibits an improved wear resistance in additionto a high lubricity.

Surprisingly it has now been found that a lubricious coating with animproved wear resistance can be obtained by using a coating formulationfor preparing a hydrophilic coating, wherein the hydrophilic coatingformulation comprises

-   -   (a) a supporting polymer comprising a backbone and at least 2        reactive moieties capable of undergoing polymerization        reactions,    -   (b) a polyelectrolyte;    -   (c) a Norrish Type I photoinitiator; and    -   (d) a Norrish Type II photoinitiator.

It has been found that the hydrophilic coatings obtainable by curing thehydrophilic coating formulation according to the invention are extremelywear resistant in tortuous tests compared to similar coatings known inthe art. For example, subjecting the coatings according to the inventionto a particulates release test, as described in the examples, results ina surprisingly low number of particles released from the coating. Thisis particularly advantageous for cardiovascular applications such asguide wires and catheters, in which the hydrophilic coating experiencesserious torture and no particle release is tolerated.

Within the context of the invention “lubricious” is defined as having aslippery surface. A coating on the outer or inner surface of a medicaldevice, such as a catheter, is considered lubricious if (when wetted) itcan be inserted into the intended body part without leading to injuriesand/or causing unacceptable levels of discomfort to the subject. Inparticular, a coating is considered lubricious if it has a friction asmeasured on a Harland FTS5000 Friction Tester (HFT) of 20 g or less,preferably of 15 g or less, at a clamp-force of 300 g, a pull speed of 1cm/s, and a temperature of 22° C. The term “wetted” is generally knownin the art and—in a broad sense—means “containing water”. In particularthe term is used herein to describe a coating that contains sufficientwater to be lubricious. In terms of the water concentration, usually awetted coating contains at least 10 wt % of water, based on the dryweight of the coating, preferably at least 50 wt %, based on the dryweight of the coating, more preferably at least 100 wt % based on thedry weight of the coating. For instance, in a particular embodiment ofthe invention a water uptake of about 300-500 wt % water is feasible.Examples of wetting fluids are treated or untreated water,water-containing mixtures with for example organic solvents or aqueoussolutions comprising for example salts, proteins or polysaccharides. Inparticular a wetting fluid can be a body fluid.

The Norrish Type I and Norrish Type II photoinitiators are used to curethe hydrophilic coating formulation according to the invention, forexample using visible light or UV, electro-beam, or gamma radiation toform the hydrophilic coating. Herein both Norrish Type I and NorrishType II photoinitiators are free-radical photoinitiators, but aredistinguished by the process by which the initiating radicals areformed. Compounds that undergo unimolecular bond cleavage of thechromophore upon irradiation to generate radicals that initiatepolymerization are termed Norrish Type I or homolytic photoinitiators. ANorrish Type II photoinitiator generates radicals indirectly by hydrogenabstraction from a suitable synergist, which may be a low molecularweight compound or a polymer.

Compounds that undergo unimolecular bond cleavage upon irradiation aretermed Norrish Type I or homolytic photoinitiators, as shown by formula

Depending on the nature of the functional group and its location in themolecule relative to the carbonyl group, the fragmentation can takeplace at a bond adjacent to the carbonyl group (α-cleavage), at a bondin the β-position (β-cleavage) or, in the case of particularly weakbonds (like C—S bonds or O—O bonds), elsewhere at a remote position. Themost important fragmentation in photoinitiator molecules is theα-cleavage of the carbon-carbon bond between the carbonyl group and thealkyl residue in alkyl aryl ketones, which is known as the Norrish TypeI reaction.

If the photoinitiator, while being in the excited state, interacts witha second molecule (a coinitiator COI) to generate radicals in abimolecular reaction as shown by formula (2), the photoinitiator istermed a NorrishType II photoinitiator. In general, the two mainreaction pathways for Norrish Type II photoinitiators are hydrogenabstraction by the excited initiator or photoinduced electron transfer,followed by fragmentation. Bimolecular hydrogen abstraction is a typicalreaction of excited diaryl ketones. Photoinduced electron transfer is amore general process, which is not limited to a certain class ofcompounds.

Examples of suitable Norrish Type I or free-radical photoinitiators arebenzoin derivatives, methylolbenzoin and 4-benzoyl-1,3-dioxolanederivatives, benzilketals, α,α-dialkoxyacetophenones, α-hydroxyalkylphenones, α-aminoalkylphenones, acylphosphine oxides,bisacylphosphine oxides, acylphosphine sulphides, halogenatedacetophenone derivatives, and the like. Commercial examples of suitableType I photoinitiators are Irgacure 2959(2-hydroxy-4′-(2-hydroxyethoxy)-2-methyl propiophenone), Irgacure 651(benzildimethyl ketal or 2,2-dimethoxy-1,2-diphenylethanone,Ciba-Geigy), Irgacure 184 (1-hydroxy-cyclohexyl-phenyl ketone as theactive component, Ciba-Geigy), Darocur 1173(2-hydroxy-2-methyl-1-phenylpropan-1-one as the active component,Ciba-Geigy), Irgacure 907(2-methyl-1-[4-(methylthio)phenyl]-2-morpholino propan-1-one,Ciba-Geigy), Irgacure 369(2-benzyl-2-dimethylamino-1-(4-morpholinophenyl)-butan-1-one as theactive component, Ciba-Geigy), Esacure KIP 150 (poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one}, FratelliLamberti), Esacure KIP 100 F (blend of poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one} and2-hydroxy-2-methyl-1-phenyl-propan-1-one, Fratelli Lamberti), EsacureKTO 46 (blend of poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one},2,4,6-trimethylbenzoyldiphenyl-phosphine oxide and methylbenzophenonederivatives, Fratelli Lamberti), acylphosphine oxides such as LucirinTPO (2,4,6-trimethylbenzoyl diphenyl phosphine oxide, BASF), Irgacure819 (bis(2,4,6-trimethylbenzoyl)-phenyl-phosphine-oxide, Ciba-Geigy),Irgacure 1700 (25:75% blend ofbis(2,6-dimethoxybenzoyl)2,4,4-trimethyl-pentyl phosphine oxide and2-hydroxy-2-methyl-1-phenyl-propan-1-one, Ciba-Geigy), and the like.Also mixtures of type I photoinitiators can be used.

Examples of Norrish Type II photoinitiators that can be used in thehydrophilic coating formulation according to the invention includearomatic ketones such as benzophenone, xanthone, derivatives ofbenzophenone (e.g. chlorobenzophenone), blends of benzophenone andbenzophenone derivatives (e.g. Photocure 81, a 50/50 blend of4-methyl-benzophenone and benzophenone), Michler's Ketone, EthylMichler's Ketone, thioxanthone and other xanthone derivatives likeQuantacure ITX (isopropyl thioxanthone), benzil, anthraquinones (e.g.2-ethyl anthraquinone), coumarin, or chemical derivatives orcombinations of these photoinitiators.

Preferred are Norrish Type I and Norrish Type II photoinitiators whichare water-soluble or can be adjusted to become water-soluble, alsopreferred photoinitiators are polymeric or polymerisablephotoinitiators.

Generally the total amount of photoinitiator in the hydrophilic coatingformulation is between 0.2 and 10 wt %, preferably between 0.8 and 8 wt%, based on the total weight of dry the coating.

Hereinafter all percentages of components given in the application arebased on the total weight of the dry coating. i.e. the hydrophiliccoating formed upon curing the hydrophilic coating formulation.

Typically the weight ratio Norrish Type I photoinitiator: Norrish TypeII photoinitiator is between 10:1 and 1:10, preferably between 5:1 and1:5.

The hydrophilic coating formulation also comprises a supporting polymercomprising a backbone and at least 2 reactive moieties capable ofundergoing polymerization reactions. Herein the supporting polymer mayalso contain hydrophilic functional groups.

Within the context of the invention the term polymer is used for amolecule comprising two or more repeating units. In particular it may becomposed of two or more monomers which may be the same or different. Asused herein, the term includes oligomers and prepolymers. Usuallypolymers have a number average weight (M_(n)) of about 500 g/mol ormore, in particular of about 1000 g/mol or more, although the M_(r), maybe lower in case the polymer is composed of relatively small monomericunits. Herein and hereinafter the M_(n) is defined as the M_(n) asdetermined by light scattering, optionally in combination with SizeExclusion Chromatography (SEC).

A supporting network can be formed upon curing said supporting polymer.The reactive moiety of the supporting polymer may be selected from thegroup consisting of radically reactive groups, such as alkenes, amino,amido, sulfhydryl (SH), unsaturated esters, such as acrylate andmethacrylate, unsaturated ethers, unsaturated amides, and alkyd/dryresins. The supporting polymer has a backbone and at least one of theabove-mentioned reactive moieties. The backbone of the supportingpolymer may be selected from the group consisting of polyethers,polyurethanes, polyethylenes, polypropylenes, polyvinyl chlorides,polyepoxides, polyamides, polyacrylamides, poly(meth)acrylics,polyoxazolidones, polyvinyl alcohols, polyethylene imines, polyesterslike polyorthoesters and alkyd copolymers, polypeptides, orpolysaccharides such as cellulose and starch or any combination of theabove. In particular, polymers with unsaturated esters, amides orethers, thiol or mercaptan groups may suitably be used in the invention.

Preferably the supporting polymer has a number average molecular weightin the range of about 750 to 20,000 g/mol, more preferably in the rangeof about 1,000 to about 15,000 g/mol, most preferably in the range ofabout 1,100 to about 10,000 g/mol, in particular in the range of about1,200 to about 7,000 g/mol, more in particular in the range of about1,400 to about 5,000 g/mol. The advantage of using a relatively highmolecular weight supporting polymer, i.e. having molecular weight ofmore than about 750 g/mol, preferably more than about 1,000 g/mol, isthat a relatively open supporting network will be formed. Such arelatively open supporting network will swell more easily and therewithprovide the coating with a higher lubricity and/or an improved dry-outtime.

The average number of reactive groups per molecule of the supportingpolymer is preferably in the range of about 1.2 to about 64, morepreferably in the range of about 1.2 to about 16, most preferably in therange of about 1.2 to about 8. This means that apart from supportingpolymer molecules comprising at least 2 reactive moieties alsosupporting polymer molecules comprising 1 reactive moiety, i.e.monofunctional polymers, may be present. The monofunctional supportingpolymers may also be part of the formed supporting network.

The supporting polymer may be used in more than 1 wt %, for example morethan 10%, more than 20 wt %, more than 30 wt % or more than 40 wt %,based on the total weight of the dry coating. The supporting polymer canbe present in the hydrophilic coating formulation up to 90 wt %,however, more often the supporting polymer will be used up to 50 or 60wt %, based on the total weight of the dry coating.

The hydrophilic coating formulation according to the invention alsocomprises a polylectrolyte. Herein a polyelectrolyte is understood to bea high molecular weight linear, branched or crosslinked polymer composedof macromolecules comprising constitutional units, in which between 5and 100% of the constitutional units contain ionized groups when thepolyelectrolyte is in the lubricious coating. Herein a constitutionalunit is understood to be for example a repeating unit, for example amonomer. A polyelectrolyte herein may refer to one type ofpolyelectrolyte composed of one type of macromolecules, but it may alsorefer to two or more different types of polyelectrolytes composed ofdifferent types of macromolecules.

The presence of a polyelectrolyte is particularly advantageous toimprove the dry-out time of the hydrophilic coating. Herein dry-out timeis defined as the duration of the hydrophilic coating remaininglubricious in the open air after the device comprising the hydrophiliccoating has been taken out of the wetting fluid wherein it has beenstored and/or wetted. Hydrophilic coatings with an improved dry-outtime, i.e. wherein the duration of the hydrophilic coating remaininglubricious is longer, will have a lower tendency of losing water anddrying out prior to insertion into the body, or in the body when itcomes in contact with e.g. a mucous membrane or vein. This may result incomplications when the device comprising the lubricious coating isinserted into the body or removed from the body. The dry-out time can bedetermined by measuring the friction in gram as a function of time thecatheter had been exposed to air on the HFT.

Considerations when selecting a suitable polyelectrolyte are itssolubility and viscosity in aqueous media, its molecular weight, itscharge density, its affinity with the supporting network of the coatingand its biocompatibility. Herein biocompatibility means biologicalcompatibility by not producing a toxic, injurous or immunologicalresponse in living mammalian tissue.

For a decreased migrateability, the polyelectrolyte is preferably apolymer having a weight average molecular weight of at least about 1000g/mol, as determinable by light scattering, optionally in combinationwith size exclusion chromatography. A relatively high molecular weightpolyelectrolyte is preferred for increasing the dry-out time and/orreduced migration out of the coating. The weight average molecularweight of the polyelectrolyte is preferably at least 20,000 g/mol, morepreferably at least 100,000 g/mol, even more preferably at least about150,000 g/mol, in particular about 200,000 g/mol or more. For ease ofapplying the coating it is preferred that the average weight is 1000,000g/mol or less, in particular 500,000 g/mol or less, more in particular300,000 g/mol or less.

Examples of ionized groups that may be present in the polyelectrolyteare ammonium groups, phosphonium groups, sulfonium groups, carboxylategroups, sulfate groups, sulfinic groups, sulfonic groups, phosphategroups, and phosphonic groups. Such groups are very effective in bindingwater. In one embodiment of the invention the polyelectrolyte alsocomprises metal ions. Metal ions, when dissolved in water, are complexedwith water molecules to form aqua ions [M(H₂O)_(x)]^(n+), wherein x isthe coordination number and n the charge of the metal ion, and aretherefore particularly effective in binding water. Metal ions that maybe present in the polyelectrolyte are for example alkali metal ions,such as Na⁺, Li⁺, or K⁺, or alkaline earth metal ions, such as Ca²⁺ andMg²⁺. In particular when the polyelectrolyte comprises quaternary aminesalts, for example quaternary ammonium groups, anions may be present.Such anions can for example be halogenides, such as Cl⁻, Br⁻, I⁻ and F⁻,and also sulphates, nitrates, carbonates and phosphates.

Suitable polyelectrolytes are for example salts of homo- and co-polymersof acrylic acid, salts of homo- and co-polymers of methacrylic acid,salts of homo- and co-polymers of maleic acid, salts of homo- andco-polymers of fumaric acid, salts of homo- and co-polymers of monomerscomprising sulfonic acid groups, homo- and co-polymers of monomerscomprising quarternary ammonium salts and mixtures and/or derivativesthereof. Examples of suitable polyelectrolytes arepoly(acrylamide-co-acrylic acid) salts, for examplepoly(acrylamide-co-acrylic acid) sodium salt,poly(acrylamide-co-methacrylic acid) salts, for examplepoly(acrylamide-co-methacrylic acid) sodium salt,poly(methacrylamide-co-acrylic acid) salts, for examplepoly(methacrylamide-co-acrylic acid) sodium salt,poly(methacrylamide-co-methacrylic acid) salts, for examplepoly(methacrylamide-co-methacrylic acid) sodium salt poly(acrylic acid)salts, for example poly(acrylic acid) sodium salt, poly(methacrylicacid) salts, for example poly(methacrylic acid) sodium salt,poly(acrylic acid-co-maleic acid) salts, for example poly(acrylicacid-co-maleic acid) sodium salt, poly(methacrylic acid-co-maleic acid)salts, for example poly(methacrylic acid-co-maleic acid) sodium salt,poly(acrylamide-co-maleic acid) salts, for examplepolyacrylamide-co-maleic acid) sodium salt,poly(methacrylamide-co-maleic acid) salts, for examplepoly(methacrylamide-co-maleic acid) sodium salt,poly(acrylamido-2-methyl-1-propanesulfonic acid) salts, poly(4-styrenesulfonic acid) salts, poly(acrylamide-co-dialkyl ammonium chloride),quaternizedpoly[bis-(2-chloroethyl)ether-alt-1,3-bis[3-(dimethylamino)propyl]urea],polyallylammonium phosphate, poly(diallyldimethylammonium chloride),poly(sodium trimethyleneoxyethylene sulfonate),poly(dimethyldodecyl(2-acrylamidoethyl) ammonium bromide), poly(2-Nmethylpyridiniumethylene iodine), polyvinylsulfonic acids, and salts ofpoly(vinyl)pyridines, polyethyleneimines, and polylysines.

Particularly suitable polyelectrolytes for use in the current inventionare copolymeric polyelectrolytes, which may be random or blockcopolymers, wherein said copolymeric polyelectrolyte is a copolymercomprising at least two different types of constitutional units, whereinat least one type of constitutional units comprises ionizable or ionizedgroups and at least one type of constitutional units is absent ofionizable or ionized groups. Herein “ionizable” is understood to beionizable in neutral aqueous solutions, i.e. solutions having a pHbetween 6 and 8. An example of such a copolymeric polyelectrolyte is apoly(acrylamide-co-acrylic acid) salt.

The hydrophilic coating composition according to the invention typicallycomprises 1-90 wt %, 3-50 wt %, 5-30 wt %, or 10-20 wt % ofpolyelectrolyte based on the total weight of the dry coating.

In one embodiment of the invention the hydrophilic coating formulationmay further comprise a non-ionic hydrophilic polymer. Herein a non-ionichydrophilic polymer is understood to be a high molecular weight linear,branched or cross-linked polymer composed of macromolecules comprisingconstitutional units, in which less than 5% of the constitutional unitscontain ionized groups when the hydrophilic polymer is in the lubriciouscoating.

The hydrophilic polymer is capable of providing hydrophilicity to acoating and may be synthetic or bio-derived and can be blends orcopolymers of both. The hydrophilic polymers include but are not limitedto poly(lactams), for example polyvinylpyrollidone (PVP), polyurethanes,homo- and copolymers of acrylic and methacrylic acid, polyvinyl alcohol,polyvinylethers, maleic anhydride based copolymers, polyesters,vinylamines, polyethyleneimines, polyethyleneoxides, poly(carboxylicacids), polyamides, polyanhydrides, polyphosphazenes, cellulosics, forexample methyl cellulose, carboxymethyl cellulose, hydroxymethylcellulose, and hydroxypropylcellulose, heparin, dextran, polypeptides,for example collagens, fibrins, and elastin, polysaccharides, forexample chitosan, hyaluronic acid, alginates, gelatin, and chitin,polyesters, for example polylactides, polyglycolides, andpolycaprolactones, polypeptides, for example collagen, albumin, oligopeptides, polypeptides, short chain peptides, proteins, andoligonucleotides.

Generally the hydrophilic polymer has a molecular weight in the range ofabout 8,000 to about 5,000,000 g/mol, preferably in the range of about20,000 to about 3,000,000 g/mol and more preferably in the range ofabout 200,000 to about 2,000,000 g/mol.

In one embodiment of the invention the hydrophilic polymer may be usedin more than 1 wt %, for example more than 10 wt %, more than 20 wt %,or more than 30 weight %, based on the total weight of the dry coating.The hydrophilic polymer can be present up to 95 wt %, however, moreoften the hydrophilic polymer will be used up to 50, 60, 70 or 80 wt %,based on the total weight of the dry coating.

In the hydrophilic coating formulation the weight ratio of the totalweight of polyelectrolyte and hydrophilic polymer to supporting polymermay for example vary between 10:90 and 90:10, such as between 25:75 and75:25 or such as between 60:40 and 40:60.

The invention relates to a hydrophilic coating formulation which whenapplied to a substrate and cured results in a hydrophilic coating.Herein a hydrophilic coating formulation refers to a liquid hydrophiliccoating formulation, e.g. a solution or a dispersion comprising a liquidmedium. Herein any liquid medium that allows application of thehydrophilic coating formulation on a surface would suffice. Examples ofliquid media are alcohols, like methanol, ethanol, propanol, butanol orrespective isomers and aqueous mixtures thereof, acetone, methylethylketone, tetrahydrofuran, dichloromethane, toluene, and aqueous mixturesor emulsions thereof or water. The hydrophilic coating formulationfurther comprises components which when cured are converted into thehydrophilic coating, and thus remain in the hydrophilic coating aftercuring. Herein curing is understood to refer to physical or chemicalhardening or solidifying by any method, for example heating, cooling,drying, crystallization or curing as a result of a chemical reaction,such as radiation-curing or heat-curing. In the cured state all or partof the components in the hydrophilic coating formulation may becross-linked forming covalent linkages between all or part of thecomponents, for example by using UV or electron beam radiation. However,in the cured state all or part of the components may also be ionicallybonded, bonded by dipole-dipole type interactions, or bonded via Van derWaals forces or hydrogen bonds.

The term “to cure” includes any way of treating the formulation suchthat it forms a firm or solid coating. In particular, the term includesa treatment whereby the hydrophilic polymer further polymerizes, isprovided with grafts such that it forms a graft polymer and/or iscross-linked, such that it forms a cross-linked polymer.

The invention also relates to a hydrophilic coating obtainable byapplying the hydrophilic coating formulation according to the inventionto a substrate and curing it. The invention further relates to alubricious coating obtainable by applying a wetting fluid to saidhydrophilic coating, and to the use of a Norrish Type I and a NorrishType II photo-initiator in a lubricious coating in order to improve itswear resistance. Further the invention relates to an article, inparticular a medical device or a medical device component comprising atleast one hydrophilic coating according to the invention and to a methodof forming on a substrate the hydrophilic coating according to theinvention.

The hydrophilic coating comprises a polyelectrolyte, optionally ahydrophilic polymer, and a supporting network, which may be ahydrophilic supporting network, and which is formed from the supportingpolymer. Said hydrophilic coating is formed by curing a hydrophiliccoating formulation comprising the polyelectrolyte, optionally thehydrophilic polymer, the supporting polymer, the Norrish Type Iphotoinitiator and the Norrish Type II photoinitiator. Preferably thepolyelectrolyte and/or the supporting network are covalently linkedand/or physically bound to each other and/or entrapped to form a polymernetwork after curing. If a hydrophilic polymer is present this may alsobe covalently linked and/or physically bound to one or more of the othercomponents and/or entrapped to form a polymer network after curing.

The fact that polyelectrolyte, optionally the hydrophilic polymer and/orthe supporting polymer are covalently and/or physically bound in thehydrophilic coating as part of a polymer network has the advantage thatthe polyelectrolyte and the hydrophilic polymer (if present) will notleak out into the environment of the hydrophilic coating, for examplewhen it is coated on a medical device. This is particularly useful whenthe medical device is inside the human or animal body.

In one embodiment of the invention a polyelectrolyte is present in awetting fluid and introduced into the hydrophilic coating when wettingthe hydrophilic coating according to the invention. This is particularlyuseful for medical devices with a hydrophilic coating which are packedin a fluid, or wherein the hydrophilic coating is wetted in a separatewetting fluid that contains the polyelectrolyte. The invention thereforealso relates to coating system for preparing a lubricious coating, saidcoating system comprising the coating formulation according to theinvention and a wetting fluid comprising a polyelectrolyte.

In one embodiment of the invention the hydrophilic coating formulationaccording to the invention further comprises at least one surfactant,which can improve the surface properties of the coating. Surfactantsconstitute the most important group of detergent components. Generally,these are water-soluble surface-active agents comprised of a hydrophobicportion, usually a long alkyl chain, attached to hydrophilic or watersolubility enhancing functional groups. Surfactants can be categorizedaccording to the charge present in the hydrophilic portion of themolecule (after dissociation in aqueous solution): ionic surfactants,for example anionic or cationic surfactants, and non-ionic surfactants.Examples of ionic surfactants include Sodium dodecylsulfate (SDS),Sodium cholate, Bis(2-ethylhexyl)sulfosuccinate Sodium salt,Cetyltrimethylammoniumbromide (CTAB), Lauryldimethylamine-oxide (LDAO),N-Lauroylsarcosine Sodium salt and Sodium deoxycholate (DOC). Examplesof non-ionic surfactants include Alkyl Polyglucosides such as TRITON™BG-10 Surfactant and TRITON CG-110 Surfactant, Branched SecondaryAlcohol Ethoxylates such as TERGITOL™ TMN Series, EthyleneOxide/Propylene Oxide Copolymers, such as TERGITOL L Series, andTERGITOL XD, XH, and XJ Surfactants, Nonylphenol Ethoxylates such asTERGITOL NP Series, Octylphenol Ethoxylates, such as TRITON X Series,Secondary Alcohol Ethoxylates, such as TERGITOL 15-S Series andSpecialty Alkoxylates, such as TRITON CA Surfactant, TRITON N-57Surfactant, TRITON X-207 Surfactant, Tween 80 and Tween 20.

In the above embodiment typically 0.001 to 1 wt % of surfactant can beapplied, preferably 0.05-0.5 wt %, based on the total weight of the drycoating.

In one embodiment of the invention the hydrophilic coating formulationaccording to the invention further comprises at least one plasticizingagent, which can enhance the flexibility of the coating, which may bepreferable when the object to be coated is likely to bend during use.Said plasticizing agent may be included in the hydrophilic coatingformulation in a concentration of from about 0.01 wt % to about 15 wt %based on the total weight of the dry coating, preferably from about 1 wt% to about 5.0 wt %. Suitable plasticizers are high boiling compounds,preferably with a boiling point at atmospheric pressure of >200° C., andwith a tendency to remain homogeneously dissolved and/or dispersed inthe coating after cure. Examples of suitable plasticizers are mono- andpolyalcohols and polyethers, such as decanol, glycerol, ethylene glycol,diethylene glycol, polyethylene glycol and/or copolymers with propyleneglycol and/or fatty acids.

The hydrophilic coating according to the invention can be coated on anarticle. The hydrophilic coating can be coated on a substrate which maybe selected from a range of geometries and materials. The substrate mayhave a texture, such as porous, non-porous, smooth, rough, even oruneven. The substrate supports the hydrophilic coating on its surface.The hydrophilic coating can be on all areas of the substrate or onselected areas. The hydrophilic coating can be applied to a variety ofphysical forms, including films, sheets, rods, tubes, molded parts(regular or irregular shape), fibers, fabrics, and particulates.Suitable surfaces for use in the invention are surfaces that provide thedesired properties such as porosity, hydrophobicity, hydrophilicity,colorisability, strength, flexibility, permeability, elongation abrasionresistance and tear resistance. Examples of suitable surfaces are forinstance surfaces that consist of or comprise metals, plastics,ceramics, glass and/or composites. The hydrophilic coating may beapplied directly to the said surfaces or may be applied to a pretreatedor coated surface where the pretreatment or coating is designed to aidadhesion of the hydrophilic coating to the substrate.

In one embodiment of the invention the hydrophilic coating according tothe invention is coated on a biomedical substrate. A biomedicalsubstrate refers, in part, to the fields of medicine, and the study ofliving cells and systems. These fields include diagnostic, therapeutic,and experimental human medicine, veterinary medicine, and agriculture.Examples of medical fields include opthalmology, orthopedics, andprosthetics, immunology, dermatology, pharmacology, and surgery;nonlimiting examples of research fields include cell biology,microbiology, and chemistry. The term “biomedical” also relates tochemicals and compositions of chemicals, regardless of their source,that (i) mediate a biological response in vivo, (ii) are active in an invitro assay or other model, e.g., an immunological or pharmacologicalassay, or (iii) can be found within a cell or organism. The term“biomedical” also refers to the separation sciences, such as thoseinvolving processes of chromatography, osmosis, reverse osmosis, andfiltration. Examples of biomedical articles include research tools,industrial, and consumer applications. Biomedical articles includeseparation articles, implantable articles, and ophthalmic articles.Ophthalmic articles include soft and hard contact lenses, intraocularlenses, and forceps, retractors, or other surgical tools that contactthe eye or surrounding tissue. A preferred biomedical article is a softcontact lens made of a silicon-containing hydrogel polymer that ishighly permeable to oxygen. Separation articles include filters, osmosisand reverse osmosis membranes, and dialysis membranes, as well asbio-surfaces such as artificial skins or other membranes. Implantablearticles include catheters, and segments of artificial bone, joints, orcartilage. An article may be in more than one category, for example, anartificial skin is a porous, biomedical article. Examples of cellculture articles are glass beakers, plastic petri dishes, and otherimplements used in tissue cell culture or cell culture processes. Apreferred example of a cell culture article is a bioreactormicro-carrier, a silicone polymer matrix used in immobilized cellbioreactors, where the geometry, porosity, and density of theparticulate micro-carrier may be controlled to optimize performance.Ideally, the micro-carrier is resistant to chemical or biologicaldegradation, to high impact stress, to mechanical stress (stirring), andto repeated steam or chemical sterilization. In addition to siliconepolymers, other materials may also be suitable. This invention may alsobe applied in the food industry, the paper printing industry, hospitalsupplies, diapers and other liners, and other areas where hydrophilic,wettable, or wicking articles are desired.

The medical device can be an implantable device or an extracorporealdevice. The devices can be of short-term temporary use or of long-termpermanent implantation. In certain embodiments, suitable devices arethose that are typically used to provide for medical therapy and/ordiagnostics in heart rhythm disorders, heart failure, valve disease,vascular disease, diabetes, neurological diseases and disorders,orthopedics, neurosurgery, oncology, opthalmology, and ENT surgery.

Suitable examples of medical devices include, but are not limited to, astent, stent graft, anastomotic connector, synthetic patch, lead,electrode, needle, guide wire, catheter, sensor, surgical instrument,angioplasty balloon, wound drain, shunt, tubing, infusion sleeve,urethral insert, pellet, implant, blood oxygenator, pump, vasculargraft, vascular access port, heart valve, annuloplasty ring, suture,surgical clip, surgical staple, pacemaker, implantable defibrillator,neurostimulator, orthopedic device, cerebrospinal fluid shunt,implantable drug pump, spinal cage, artificial disc, replacement devicefor nucleus pulposus, ear tube, intraocular lens and any tubing used inminimally invasive surgery.

Articles that are particularly suited to be used in the presentinvention include medical devices or components such as catheters, forexample intermittent catheters, balloon catheters, PTCP catheters, stentdelivery catheters, guide wires, stents, syringes, metal and plasticimplants, contact lenses and medical tubing.

The hydrophilic coating formulation can be applied to the substrate byfor example dip-coating. Other methods of application include spray,wash, vapor deposition, brush, roller and other methods known in theart.

The concentration of ionic or ionizable groups in the hydrophiliccoating and the thickness of the hydrophilic coating according to theinvention may be controlled by altering the type of polyelectrolyte,polyelectrolyte concentration in the hydrophilic coating formulation,soaking time, drawing speed, viscosity of the hydrophilic coatingformulation and the number of coating steps. Typically the thickness ofa hydrophilic coating on a substrate ranges from 0.1-300, preferably0.5-100 μm, more preferably 1-30 μm.

The invention further relates to a method of forming on a substrate ahydrophilic coating which has a low coefficient of friction when wettedwith a water-based liquid, wherein said hydrophilic coating comprises anpolyelectrolyte.

To apply the hydrophilic coating on the substrate, a primer coating maybe used in order to provide a binding between the hydrophilic coatingand the substrate. The primer coating is often referred to as theprimary coating, base coat or tie coat. Said primer coating is a coatingthat facilitates adhesion of the hydrophilic coating to a givensubstrate, as is described in for example WO02/10059. The bindingbetween the primer coating and the hydrophilic coating may occur due tocovalent or ionic links, hydrogen bonding, physisorption or polymerentanglements. These primer coatings may be solvent based, water based(latexes or emulsions) or solvent free and may comprise linear, branchedand/or cross-linked components. Typical primer coatings that could beused comprise for example polyether sulfones, polyurethanes, polyesters,including polyacrylates, as described in for example U.S. Pat. No.6,287,285, polyamides, polyethers, polyolefins and copolymers of thementioned polymers.

In particular, the primer coating comprises a supporting polymernetwork, the supporting network optionally comprising a functionalhydrophilic polymer entangled in the supporting polymer network asdescribed in WO2006/056482 A1. The information with respect to theformulation of the primer coating is herewith incorporated by reference.

A primer coating as described above is in particular useful forimproving adherence of a coating comprising a hydrophilic polymer suchas a polylactam, in particular PVP and/or another of the aboveidentified hydrophilic polymers, in particular on polyvinylchloride(PVC), silicone, polyamide, polyester, polyolefin, such as polyethylene,polypropylene and ethylene-propylene rubber (e.g. EPDM), or a surfacehaving about the same or a lower hydrophilicity.

In general there is no restriction as to the thickness of the primercoating, but typically the thickness is less than 5 μm, less than 2 μmor less than 1 μm.

In an embodiment, the surface of the article is subjected to oxidative,photo-oxidative and/or polarizing surface treatment, for example plasmaand/or corona treatment in order to improve the adherence of the coatingwhich is to be provided. Suitable conditions are known in the art.

Application of the formulation of the invention may be done in anymanner. Curing conditions can be determined, based on known curingconditions for the photo-initiator and polymer or routinely bedetermined.

In general, curing may be carried out at any suitable temperaturedepending on the substrate, as long as the mechanical properties oranother property of the article are not adversely affected to anunacceptable extent.

Intensity and wavelength of the electromagnetic radiation can routinelybe chosen based on the photoinitiator of choice. In particular, asuitable wavelength in the UV, visible or IR part of the spectrum may beused.

The invention will be further illustrated by the following examples.

EXAMPLES

A primer coating formulation was prepared as indicated below.

Primer coating formulation (Examples 1 and 2 and Comparative ExperimentsA and B PTGL1000(T-H)₂ * 5.00% (w/w) Irgacure 2959 (Aldrich) 0.20% (w/w)Ethanol (Merck, 96% extra pure PH EUR, BP) 94.8% (w/w) * Synthesized asdescribed below

The above mentioned components were added to a brown colored glass flaskand mixed overnight (˜16 hours) at room temperature. The next morningthe primer formulation was a homogeneous liquid with a viscosity of 7mPa·s. Herein the viscosity was measured on a Brookfield CAP1000, v.1.2in combination with cone nr. 1 at 25° C.

The above primer coating formulation was applied to Pebax® 7233 cathetertubing (shafts) with an outer diameter of 0.034″ (0.86 mm) using aHarland 175-24 PCX coater. The application parameters were used aslisted in Table 1.

TABLE 1 Application conditions of the primer coating formulation Primercoating formulation Solids primer [w/w %] 5 Viscosity [mPa · s] 7 Drawspeed primer [cm/s] 1.0 Cure time primer [s] 15

Synthesis of PTGL1000(T-H)₂

In a dry inert atmosphere toluene diisocyanate (TDI or T, Aldrich, 95%purity, 87.1 g, 0.5 mol), Irganox 1035 (Ciba Specialty Chemicals, 0.58g, 1 wt % relative to hydroxy ethyl acrylate (HEA or H)) and tin(II)2-ethyl hexanoate (Sigma, 95% purity, 0.2 g, 0.5 mol) were placed in a 1liter flask and stirred for 30 minutes. The reaction mixture was cooledto 0° C. using an ice bath. HEA (Aldrich, 96% purity, 58.1 g, 0.5 mol)was added dropwise in 30 min, after which the ice bath was removed andthe mixture was allowed to warm up to room temperature. After 3 h thereaction was complete.Poly(2-methyl-1,4-butanediol)-alt-poly(tetramethyleneglycol) (PTGL1000,Hodogaya, M_(n)=1000 g/mol, 250 g, 0.25 mol) was added dropwise in 30min. Subsequently the reaction mixture was heated to 60° C. and stirredfor 18 h, upon which the reaction was complete as indicated by GPC(showing complete consumption of HEA), IR (displayed no NCO relatedbands) and NCO titration (NCO content below 0.02 wt %).

Example 1

A hydrophilic coating formulation (1) was prepared comprising both aNorrish Type I (Irgacure 2959) and a Norrish Type II (benzophenone)photoinitiator.

PEG4000DA * 2.00 wt % Polyvinylpyrollidone (PVP, 1.3M, Aldrich) 1.33 wt% Poly(acrylamide-co-acrylic acid) partial sodium salt 0.67 wt % (14.5wt % of Na⁺), 20 wt % acrylamide, M~200,000 (PAcA) (Aldrich)Benzophenone (Aldrich) 0.08 wt % Irgacure 2959 0.04 wt % Tween 80(surfactant, Merck) 0.04 wt % Water 47.92 wt %  MeOH (Merck pa) 47.92 wt%  * Synthesized as described below

Comparative Experiment A

For comparison hydrophilic coating formulation A was prepared withoutNorrish Type II photoinitiator.

PEG4000DA * 2.00 w % PVP 1.33 w % PAcA 0.67 w % Benzophenone — Irgacure2959 0.04 w % Tween 80 0.04 w % Water 47.96 w %  MeOH 47.96 w %  *Synthesized as described below

The above mentioned components of Example 1 and Comparative Experiment Awere added to brown colored glass flasks and mixed overnight (˜16 hours)at room temperature. The next morning the hydrophilic coatingformulations were homogeneous liquids with a viscosity as indicated inTable 2. Herein the viscosity was measured on a Brookfield CAP1000,v.1.2 in combination with cone nr. 1 at 25° C.

Synthesis of PEG4000DA

150 g (75 mmol OH) of polyethyleneglycol (PEG4000, Biochemika Ultra fromFluke, OH value 28.02 mg KOH/g, 499.5 mew/kg, M_(n)=4004 g/mol) wasdissolved in 350 ml of dry toluene at 45° C. under nitrogen atmosphere.0.2 g (0.15 wt %) of Irganox 1035 was added as a radical stabilizer. Theresulting solution was distilled azeotropically overnight (50° C., 70mbar) leading the condensed toluene over 4 Å mol sieves. For each batchof PEG the OH value was accurately determined by OH titration, which wasperformed according to the method described in the 4^(th) edition of theEuropean Pharmacopoeia, paragraph 2.5.3, Hydroxyl Value, page 105. Thismade it possible to calculate the amount of acryloyl chloride to beadded and to determine the degree of acrylate esterification during thereaction. 9.1 g (90 mmol) of triethylamine was added to the reactionmixture, followed by a dropwise addition of 8.15 g (90 mmol) of acryloylchloride dissolved in 50 ml of toluene in 1 h. Triethylamine andacryloyl chloride were colorless liquids. The reaction mixture wasstirred for 2 to 4 h at 45° C. under nitrogen atmosphere. During thereaction the temperature was kept at 45° C. to prevent crystallizationof PEG. To determine the conversion a sample was withdrawn from thereaction mixture, dried and dissolved in deuterated chloroform.Trifluoro acetic anhydride (TFAA) was added and a ¹H-NMR spectrum wasrecorded. TFAA reacts with any remaining hydroxyl groups to form atrifluoro acetic ester, which can be easily detected using ¹H-NMRspectroscopy (the triplet signal of the methylene protons in theα-position of the trifluoro acetic acid group (g, 4.45 ppm) can beclearly distinguished from the signal of the methylene groups in theα-position of the acrylate ester (d, 4.3 ppm)). At a degree of acrylateesterification lower than 98% an additional 10 mmol of acryloyl chlorideand triethylamine were added to the reaction mixture allowing it toreact for 1 h. At a degree of acrylate esterification higher than 98%the warm solution was filtered to remove triethylamine hydrochloridesalts. Approximately 300 ml of toluene was removed under vacuum (50° C.,20 mbar). The remaining solution was kept at 45° C. in a heated droppingfunnel and added dropwise to 1 liter of diethyl ether (cooled in an icebath). The ether suspension was cooled for 1 h before PEG4000DA wasobtained by filtration. The product was dried overnight at roomtemperature under reduced air atmosphere (300 mbar). Yield: 80-90% aswhite crystals.

The hydrophilic coating formulations of Example 1 and ComparativeExperiment A were applied on the Pebax® 7233 shafts with primer coatingusing a Harland 175-24 PCX coater. The relevant application conditionsused are represented in Table 2.

TABLE 2 Application conditions for hydrophilic coating formulations ofExample 1 and Comparative Experiment A 1 A Solids topcoat [w/w %] 4 4Viscosity [mPa · s] 23 24 Draw speed topcoat [cm/s] 1.0 1.0 Cure timetopcoat [s] 350 360

The coated length of the Pebax catheter shafts was 27 cm for the primercoating and the hydrophilic coating.

On average the UV light intensity in the PCX coater is 60 mW/cm² between250-400 nm, measured with a Harland UVR335 (IL1400) light meter incombination with detector SED005#989 and filter WBS320#27794. The primercoating was exposed 15 seconds, while the topcoat was exposed 360seconds to the UV light. This correspondings with a UV-dose ofrespectively 0.9 J/cm² and 21.6 J/cm². During the application thetemperature was 21° C. and 50% RH. For applied coating parameters seeTable 3,

TABLE 3 Applied process parameters in PCX coater Harland Coatingparameters selection table Hydrophilic Primer coating Units DippingCycle Move device carrier to position 134.5 134.5 Cm speed 6.5 6.5cm/sec acceleration time 0.1 0.1 Sec Operator Prompt “Remove dip cover”Operator Prompt “Switch funnels” Move device carrier down 24.5 24.5 Cmspeed 4 4 cm/sec acceleration time 0.1 0.1 cm/sec/sec Operator PromptCheck alignment of the devices above the funnels Move device carrierdown 27 27 Cm speed 2 2 0 cm/sec acceleration time 0.1 0.1 Sec TimePause 10 10 Sec Move device carrier up 30 30 speed 1.0 1.0 cm/secacceleration time 0.1 0.1 Sec Wove device carrier to position 170 170 CmSpeed 6.5 6.5 cm/sec acceleration time 0.1 0.1 Sec Operator Prompt“Close doors” Cure Cycle Rotator On 4 4 Rpm UV lights Full Power E-G andL-N Time pause 15 360 Sec Close Shutter JV lights Standby Power E-G andL-N Rotator Off

The coated catheter shafts were tested in a particulate release test asdescribed below.

Sample Preparation for Particulates Release Test

10 g of Congo-red was weighed and dissolved in 1 L of milli-Q purifiedwater in a measuring flask. The resulting 1 wt % Congo-red solution wasused to dye the hydrophilic coatings on the coated Pebax™ cathetershafts. The coated catheter shafts were impregnated in this solution for30 minutes. The coated catheter shafts were air dried for 15 minutes.Wetting again in purified water was performed to remove the excess ofCongo-red. Now the coated catheter shafts were air dried again to anextend that they showed no stickiness (approximately 1 hour). Thecongo-red coloured coated catheter shafts were exposed to the wear testdescribed below.

Particulates Release Wear Test

The particulates release wear test was conducted on a Zwick 1474ZmartPro tensile tester with 10N KAP-Z loadcell (hereinafter referred toas “Zwick tensile tester”, see FIG. 1). The following materials andset-up were used:

-   -   950 mm of 0.022″ (0.56 mm) Nitinol SE metal guide wire (diameter        0.0022″, New England Precision Grinding) as reinforcing core        wire inside each coated catheter shaft.    -   625 mm top-part of Medtronic Pro-Flo 6F pigtail 2.00 mm, 110 cm,        cardio-vascular angiographic catheter (hereinafter referred to        as “Pro-Flo guiding catheter” or, in FIG. 1, “Pro-Flo guiding        catheter”) as outer counter surface for the wear test. The        connector on the proximal end was used to connect a syringe.    -   60 ml of Milli-Q water    -   Mould to support the outer catheter in the Zwick 1474 ZmartPro        tensile tester. The mould has a 180° C. curvature of Ø40 mm    -   150 mm of coated catheter shaft (in FIG. 1: “colored CV catheter        shaft”) as described above.

The coated catheter shaft was glued onto the Nitinol guide wire usingLoctite, to prevent sliding of the coated catheter shaft during testing,200 mm from the end of the Nitinol guide wire (from the load cell). Thisensured that the coated catheter shaft was placed just before enteringthe Ø 40 mm curvature when inserting into the test set-up (see FIG. 1).The coated catheter shaft was placed in milli-Q water for 30 seconds toensure proper wetting of the hydrophilic coating. During wetting of thesample for 30 seconds, the Congo-red indicator partly dissolved in thewater. The Nitinol guide wire and the glued coated catheter shaft wereinserted into the straightened and pre-wetted Pro-Flo guiding catheter,at the catheter entrance part. The Pro-Flo guiding catheter and theinserted coated catheter shaft were placed in the polymer supportingmould, with the specific 180° curvature of 40 mm, and extra milli-Qwater was carefully flushed into the Pro-Flo guiding catheter to ensurecomplete wetting of the inner space.

The polymer mould and Pro-Flo guiding catheter comprising the insertedcoated catheter shaft were placed into the Zwick tensile tester andattached to the load cell by a clamp, which was placed 350 mm above thetop of the mould. The end part of the catheter shaft was now inside thePro-Flo guiding catheter just before entering the curvature wherefriction (and wear) mainly takes place.

Using the Zwick tensile tester, the coated catheter shaft was insertedover a length of 100 mm and withdrawn over the same length with a speedof 200 mm/min. One insertion and withdrawal is defined as 1 cycle. Eachsample was conducted to the test during 5 cycles.

Particulates Collection

After the particulates release wear test as described above, one side ofthe Pro-Ho guiding catheter was released from the mould and placed abovea jar collecting the milli-Q water out of the Pro-Flo guiding catheter.A syringe, containing 10 ml of milli-Q water was attached to thecatheter entrance part of the Pro-Flo guiding catheter, flushing thePro-Flo guiding catheter. The Nitinol guide wire and attached coatedcatheter shaft were removed and flushed with 10 ml of milli-Q water. ThePro-Flo guiding catheter was flushed with 4×10 ml of milli-Q water. The60 ml of collected milli-Q water was subjected to particulatesmeasurements (see below), while the Pro-Flo guiding catheter was driedfor further visual check of contamination with coloured particles. Noparticles were found.

A 0.45-micron filter Millipore type HAWP was used to filtrate thecollected milli-Q water solution. With this filter also particlessmaller than 10 micron are collected, while such small particles do notneed to be included in the counting according to the USP28 standard.However, the image analysis as described below could clearly distinguishbetween sizes bigger and smaller than 10 micron. A Millipore glassBüchner funnel system was used for this procedure.

The filter was wetted with pure water first to make sure the filter didnot colour red too much. A slightly pink colour could not be prevented.This background colour was corrected with the white and colour balance.This correction did not affect the final result.

Imaging

Microscopy images were recorded using a LEICA MA FLIII equipped with aCC-12 Soft Imaging System. The filter was illuminated in 180°backscattering mode with a LEICA CLS 150× with light guides fixed to themicroscope. The upper switch was set on value 4 and the lower was set atposition 6. A 10× ocular was used and the zoom factor was 5. The whitebalance was auto set using white paper. The illumination time per photocapture was set at 3.900 ms. The filter was partially imaged with 9photos in total representing an area of 2.71×2.12 mm equals 5.7 mm²each. A piece of paper with a grid of 9 sections was placed under thefilter enabling to record images out of every section. The total filtersurface is 1020 mm². The correction factor for the total filter is10201(9×5.75)=20.

Image Analysis

The image analysis comprised the following steps:

-   -   Background subtraction    -   Object analysis    -   Data visualization

Due to a varying background due to variation in Congo-red dye absorptionby the filter, a background correction had to be Performed.

Opening the image in Bersoft imaging software “Image MeasurementProfessional 4.02” and taking a pixel slice through the center revealedthe background curvature. The following procedure was used: a verticaland a horizontal slice were taken through the approximate center of theimage. The pixel values were exported to Excel, wherein a fit was madeof both slices.

The quadratic curves were then used in a Mathematica Workbook tosubtract the background (see code below).

Mathematica code used for the background subtraction.fMain=Import[“D:\\image.jpg”]; fTotal=fMain;{n1,n2,n3}=Dimensions[fMain[[1,1]]]; nx=n1; ny=n2; (*-- Fit of Redbackground--*) tabelRed=Table[fMain[[1,1,x,y,1]],{x,nx},{y,ny}];(*---Generate table t.b.v. “Fit”. *)tabelFit=Flatten[Table[{x,y,tabelRed[[x,y]]},{x,nx},{y,ny}],1];(*---Fit, calculate parameters. *) opl=Fit[tabelFit,{1,x,x{circumflexover ( )}2,y,y{circumflex over ( )}2},{x,y}]; r0=opl[[1]];{r1,r2,r3,r4}=Table[opl[[i,1]],{i,2,5}];Print[“pLijst=”,{r0,r1,r2,r3,r4}]; tabelRed=. tabelFit=.fTotal[[1,1]]=Table[{Abs[(fMain[[1,1,i,j,3]]−(r0+r1*i+r2*i{circumflexover ( )}2+r3*j+         r4*j{circumflex over ( )}2)−10)*2−40],0,0},{i,n1},{j,n2}]; Export[“D:\\BackgroundRSubtracted.jpg”,fTotal,“JPEG”];fTotal=. fMain=. opl=.

All RGB colours were combined to one value and put in RGB Red. Theresulting picture was saved as a JPG file. The image was then opened inBersoft imaging software to detect all objects which had a RGB Red pixelvalue above 24. The level was chosen such that it is just above theremaining overall background value.

After analysing all objects, the data was exported to Excel wherein thevisualization is done. The result of all nine images was put togetherand corrected for the fraction of the total filter surface.

Interpretation

Particles were analysed on the filter. Particles which were smaller than10 micron in all directions were ignored according to the USP28.Particles which were larger than 10 micron in at least one directionwere counted and related to the USP28 standard. Particle surfaces wereconverted to particle volumes, assuming that the particles were rigidspheres. It was taken into account that the catheter has a coatingthickness of 2 micron.

Criteria:

Particles >10 micron (particle volume between 500 μm³ and 8000 μm³):less than 3000 per release test (=per filter).Particles >25 micron (particle volume >8000 μm³): less than 300 perrelease test (=per filter).

Particulate Release Wear Test Results of Example 1 and ComparativeExample A

The hydrophilic coatings 1 and A on the catheter shafts were bothsubjected to the particulates release wear test as described above. Theparticulates release of these two coatings is represented in Table 4.

TABLE 4 Particulates count related to the USP criteria Sample >10micron >25 micron Passed Example 1 80 20 Yes Comparative 6340 1260 Noexample A

A significant reduction in particulates release was obtained due to theaddition of a Norrish Type II photoinitiator (benzophenone).

1.-18. (canceled)
 19. Coating formulation for preparing a hydrophiliccoating, wherein the hydrophilic coating formulation comprises (a) asupporting monomer and/or polymer comprising at least 2 reactivemoieties capable of undergoing polymerization reactions; wherein thesupporting polymer has a number average molecular weight in the range750-20,000 g/mol, preferably 1,000-15,000 g/mol, more preferably1,100-10,000, in particular 1,200-7,000, more in particular 1,400-5,000g/mol; (b) a polyelectrolyte; (c) a Norrish Type I photoinitiator; and(d) a Norrish Type II photoinitiator
 20. Coating formulation accordingto claim 19, wherein the Norrish Type I photoinitiator is chosen fromthe group consisting of benzoin derivatives, methylolbenzoin and4-benzoyl-1,3-dioxolane derivatives, benzilketals,α,α-dialkoxyacetophenones, α-hydroxy alkylphenones,α-aminoalkylphenones, acylphosphine oxides, bisacylphosphine oxides,acylphosphine sulphides, and halogenated acetophenone derivatives. 21.Coating formulation according to claim 19, wherein the Norrish Type IIphotoinitiator is chosen from the group consisting of aromatic ketonessuch as benzophenone, xanthone, derivatives of benzophenone (e.g.chlorobenzophenone), blends of benzophenone and benzophenone derivatives(e.g. Photocure 81, a 50/50 blend of 4-methyl-benzophenone andbenzophenone), Michler's Ketone, Ethyl Michler's Ketone, thioxanthoneand other xanthone derivatives like Quantacure ITX (isopropylthioxanthone), benzil, anthraquinones (e.g. 2-ethyl anthraquinone),coumarin, or chemical derivatives or combinations of thesephotoinitiators.
 22. Coating formulation according to claim 19, whereinthe supporting polymer comprises a backbone selected from the groupconsisting of polyethers, polythioethers, polyurethanes, polyethylenes,polypropylenes, polyvinyl chlorides, polyepoxides, polyamides,polyacrylamides, poly(meth)acrylics, polyoxazolidones, polyvinylalcohols, polyethylene imines, polyesters like polyorthoesters and alkydcopolymers, polypeptides, and polysaccharides such as cellulose andstarch or any combination of the above and at least 2 reactive moietiesselected form the group consisting of radically reactive groups, such asalkenes, amino, amido, sulfhydryl (SH), unsaturated esters such asacrylate and methacrylate, unsaturated ethers, unsaturated amides, andalkyd/dry resins.
 23. Coating formulation according to claim 19, whereinthe polyelectrolyte is chosen from the group consisting of salts ofhomo- and co-polymers of acrylic acid, salts of homo- and co-polymers ofmethacrylic acid, salts of homo- and co-polymers of maleic acid, saltsof homo- and co-polymers of fumaric acid, salts of homo- and co-polymersof sulfonic acid, quarternary ammonium salts and mixtures and/orderivatives thereof.
 24. Coating formulation according to claim 23,wherein the polyelectrolyte is a polyacrylamide-co-acrylic acid) salt.25. Hydrophilic coating obtainable by curing a hydrophilic coatingformulation according to claim
 19. 26. Lubricious coating obtainable byapplying a wetting fluid to a hydrophilic coating according to claim 25.27. Lubricious coating having a wear resistance, as measured accordingto the particulates release wear test, corresponding to less than 3000,preferably less than 2000, more preferably less than 1000, in particularless than 500 particles larger than 10 μm.
 28. Coating system forpreparing a lubricious coating, said coating system comprising a coatingformulation according to claim 19 and a wetting fluid comprising apolyelectrolyte.
 29. Use of a Norrish Type I and a Norrish Type IIphoto-initiator in a lubricious coating wherein the wear resistance, asmeasured as measured according to the particulates release wear test,corresponding to less than 3000, preferably less than 2000, morepreferably less than 1000, in particular less than 500 particles largerthan 10 μm.
 30. Article comprising at least one hydrophilic coating orlubricious coating according to claim
 25. 31. Article according to claim30, wherein the article is a medical device or component.
 32. Medicaldevice or component according to claim 31 comprising a catheter, amedical tubing, a guide wire, a stent, or a membrane.
 33. Method offorming on a substrate a hydrophilic coating, the method comprisingapplying a coating formulation according to claim 19 to at least onesurface of the article; and allowing the coating formulation to cure byexposing the formulation to electromagnetic radiation thereby activatingthe initiator.